Michael A. Johnson
- Associate Professor
2030 Becker Dr
Lawrence, KS 66047-1620
- Analytical Chemistry
- Bioanalytical Chemistry
Bioanalytical chemistry; microsensor development; microfluidics; electrochemical detection of neurotransmitters; fluorescence microscopy; neurological disorders; oxidative stress.
The goal of my research program is the development and application of bioanalytical techniques for studying how neurons communicate with each other. A wide array of techniques are employed, including fluorescence microscopy, caged compound photolysis, microfluidics, biochemical methods, behavioral techniques, and state-of-the-art electrochemical techniques that allow for the monitoring of biogenic molecules on physiologically relevant time scales. These methods are used to study a variety of important problems, including neurological disorders, oxidative stress, and mechanisms of drug action.
Huntington’s disease. Huntington’s disease (HD) is a neurodegenerative disorder characterized by uncontrollable muscle movements and mental illness. HD patients typically die 15 to 20 years following symptom onset. We and others have recently discovered that release of dopamine, a key neurotransmitter in motor and cognitive signaling, is sharply attenuated in animal models of HD. To understand the contributions of abnormal neurotransmitter release in the debilitating motor symptoms of HD, electrochemical techniques have been applied in vivo to animal models of HD. Additionally, microscopy techniques are applied to study tissue sections in these animal models to yield clues regarding mechanisms of altered signaling.
Chemobrain. “Chemobrain” is a decline in cognitive function experienced by patients undergoing chemotherapy treatment. Recent studies comparing cognitive function before and after chemotherapy suggest that approximately 20-30% of cancer patients will exhibit lower cognitive performance after chemotherapy than would be expected. Developing an understanding of chemobrain is becoming more important as the survival rates of cancers continue to increase. We are currently employing electrochemical and behavioral techniques in order to unravel the underlying mechanisms of chemobrain.
Oxidative Stress and Neurotransmission. A strong connection has been established between oxidative stress and many neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, and Lou Gehrig’s disease. We are interested in the effects of oxidative stress on neuronal function. Electrochemical and microscopy techniques are used to characterize release and uptake processes in models of oxidative stress.
Caged Compound Photolysis. Our research group is combining caged compound photolysis with fast-scan cyclic voltammetry measurements in order to resolve neurotransmitter interactions. Caged compounds are molecules that can release a molecular ‘cage’ upon exposure to light of sufficient energy. Here, we make use of the p-hydroxyphenacyl and coumarin cages to render bioactive molecules inactive. We then use a microscopy or a fiber-optic cable to supply ultraviolet and visible light in order to bioactivate the molecule on millisecond timescales. Immediate changes in neurotransmitter release are monitored using fast-scan cyclic voltammetry.
Microfluidic devices. We are pursuing the development and use of microfluidic devices for the study of neurotransmitter/neuromodulator release from brain slices. This approach will be combined with caged compound photoactivation as well.
Selected Publications —
Tian, J., Stucky, C.S., Wang, T., Muma, N.A., Johnson, M., and Du, H. Mitochondrial Dysfunction Links to Impaired Hippocampal Serotonin Release in a Mouse Model of Alzheimer’s Disease. J. Alzheimers Dis. 2023; 93(2):605-619. doi: 10.3233/JAD-230072
Jarosova, R.; Woolfolk, S.K.; Martinez-Rivera, N.; Jaeschke, M.W.; Rosa-Molinar, E.; Tamerler, C.; Johnson, M.A. Spatiotemporal Imaging of Zinc Ions in Zebrafish Live Brain Tissue Enabled by Fluorescent Bionanoprobes. Molecules 2023, 28(5), 2260. https://doi.org/ 10.3390/molecules28052260
Jarosova, R., Niyangoda, S.S., Hettiarachchi, P., and Johnson, M.A., Impaired Dopamine Release and Latent Learning in Alzheimer's Disease Model Zebrafish. ACS Chemical Neuroscience 2022 13 (19), 2924-2931 DOI: 10.1021/acschemneuro.2c00484
Hettiarachchi, P., and Johnson, M.A., Characterization of D3 Autoreceptor Function in Whole Zebrafish Brain with Fast-Scan Cyclic Voltammetry. ACS Chemical Neuroscience 2022 13 (19), 2863-2873 DOI: 10.1021/acschemneuro.2c00280
Hettiarachchi, P., and Johnson, M.A. Characterization of D3 Autoreceptor Function in Whole Zebrafish Brain with Fast-Scan Cyclic Voltammetry. ACS Chem. Neurosci. 2022, 13, 2863-2873. DOI: 10.1021/acschemneuro.2c00280
Jarosova, R., Niyangoda, S.S., Hettiarachchi, P., and Johnson, M.A. Impaired Dopamine Release and Latent Learning in Alzheimer’s Disease Model Zebrafish. ACS Chem. Neurosci. 2022, 13, 2924-2931. DOI: 10.1021/acschemneuro.2c00484
Hettiarachchi, P., Niyangoda, S.S., Jarosova, R., and Johnson, M.A., Dopamine Release Impairments Accompany Locomotor and Cognitive Deficiencies in Rotenone-Treated Parkinson's Disease Model Zebrafish. Chem. Res. Toxicol. 2022, 35, 11, 1974-1982. DOI: 10.1021/acs.chemrestox.2c00150
Chase Stucky and Michael A. Johnson, Improved Serotonin Measurement with Fast-Scan Cyclic Voltammetry: Mitigating Fouling by SSRIs. 2022 J. Electrochem. Soc. 169 045501.
Jarosova R., Douglass A.D., and Johnson M.A.*, Optimized Sawhorse Waveform for the Electrochemical Measurement of Oxytocin Release in Zebrafish. Anal. Chem., 2022 94(6), 2942-2949.
Jarosova R. and Johnson M.A.*, In Situ Electrochemical Monitoring of Caged Compound Photochemistry: An Internal Actinometer for Substrate Release.Anal. Chem., 2021. 93(5): 2776-2784.
Jarmolowicz D.P., Gehringer R.C., Lemley S.M., Sofis M.J., Kaplan S.V., Johnson M.A.*5-Fluorouracil impairs attention and dopamine release in rats. Behav. Brain Res. 2019, 362, 319-322.
Kaplan S.V., Limbocker R.A., Levant B., Johnson M.A.* Regional differences in dopamine release in R6/2 Huntington’s disease model mice. Electroanalysis 2018, 30(6):1066-1072.
Field T.M., Shin M., Stucky C.S., Loomis J., Johnson M.A.* Electrochemical Measurement of Dopamine Release and Uptake in Zebrafish Following Treatment with Carboplatin. ChemPhysChem 2018, 19(10):1192-1196.
Shin M., Field T.M., Furgerson M.N., Stucky C.S., Johnson M.A.* Dopamine release and uptake in zebrafish whole brain ex vivo. ACS Chem Neurosci. 2017, 8(9):1880-1888.
Sofis M.J., Jarmolowicz D.P., Kaplan S.V., Gehringer R.C., Lemley S.M., Garg G., Blagg B.S., Johnson M.A. KU32 prevents 5-fluorouracil induced cognitive impairment. Behav Brain Res. 2017, 329:186-190.
Kaplan S.V., Limbocker R.A., Divis J.L., Osterhaus G.L., Newby M.D., Sofis M.J., Jarmolowicz D.P., Newman B.D., Mathews T.A., Johnson M.A.* Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carboplatin. ACS Chem. Neurosci. 2016, 7(6):689-699. Note: ACS Editor’s Choice Award, Featured on the journal cover, Featured in Chemical & Engineering News, 94(21), May 23, 2016.
Shin M., Kaplan S.V., Raider K.D., Johnson M.A.* Simultaneous measurement and quantitation of 4-hydroxyphenylacetic acid and dopamine with fast-scan cyclic voltammetry. Analyst. 2015, 140(9):3039-3047.
Sun, M., Johnson, M.A.* Measurement of total antioxidant capacity in sub-μL blood samples using craft paper-based analytical devices. RSC Advances. 2015, 5(69):55633-55639.